Chemokine (C-C Motif) receptor 1 is required for efficient recruitment of neutrophils during respiratory infection with modified vaccinia virus Ankara
| Autor: | Carsten J. Kirschning, Philip J. R. Price, Christine Brandmüller, Lino E. Torres-Domínguez, Bruno Luckow, Michael H. Lehmann, Gerd Sutter, Julia Zorn |
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| Rok vydání: | 2014 |
| Předmět: |
CCR1
Male Leukocyte migration Chemokine Neutrophils viruses Immunology Medizin Receptors CCR1 Cellular Response to Infection Vaccinia virus Microbiology complex mixtures chemistry.chemical_compound Mice Virology Vaccinia Animals Humans CXC chemokine receptors Orthopoxvirus Lung Respiratory Tract Infections Cells Cultured Mice Knockout Innate immune system biology Respiratory infection hemic and immune systems biology.organism_classification Toll-Like Receptor 2 Mice Inbred C57BL chemistry Insect Science biology.protein Female |
| Zdroj: | Journal of virology. 88(18) |
| ISSN: | 1098-5514 |
| Popis: | Modified vaccinia virus Ankara (MVA) serves as a versatile platform in vaccine development. This highly attenuated orthopoxvirus, which cannot replicate in mammalian cells, triggers strong innate immune responses, including cell migration. Previously, we have shown that induction of chemokine (C-C motif) ligand 2 (CCL2) by MVA is necessary for the recruitment of monocytes and T cells, but not neutrophils, to the lung. Here, we identified neutrophil-attracting chemokines produced by MVA-infected primary murine lung fibroblasts and murine bone marrow-derived macrophages. We demonstrate that MVA, but not vaccinia virus (VACV) strain WR, induces chemokine expression, which is independent of Toll-like receptor 2 (TLR2) signaling. Additionally, we show that both chemokine (C-C motif) receptor 1 (CCR1) and chemokine (C-X-C motif) receptor 2 (CXCR2) are involved in MVA-induced neutrophil chemotaxis in vitro . Finally, intranasal infection of Ccr1 −/− mice with MVA, as well as application of the CCR1 antagonist J-113863, revealed a role for CCR1 in leukocyte recruitment, including neutrophils, into the lung. IMPORTANCE Rapid attraction of leukocytes to the site of inoculation is unique to MVA in comparison to other VACV strains. The findings here extend current knowledge about the regulation of MVA-induced leukocyte migration, particularly regarding neutrophils, which could potentially be exploited to improve other VACV strains currently in development as oncolytic viruses and viral vectors. Additionally, the data presented here indicate that the inflammatory response may vary depending on the cell type infected by MVA, highlighting the importance of the site of vaccine application. Moreover, the rapid recruitment of neutrophils and other leukocytes can directly contribute to the induction of adaptive immune responses elicited by MVA inoculation. Thus, a better understanding of leukocyte migration upon MVA infection is particularly relevant for further development and use of MVA-based vaccines and vectors. |
| Databáze: | OpenAIRE |
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